The objective of the proposed research is an elucidation of how alterations in various peripheral and central neural and humoral factors interact to establish breath-by-breath modulations of airway smooth muscle tone. Of especial interest is a determination of how feed-back information from pulmonary stretch receptor afferents regulate airway tone. A comparison will be made of responses of airway muscle to prolonged stimulation in vivo and in vitro. Conditions of hyperventilation and hypoventilation will be combined with acute and chronic hypoxia, hypercapnea, hypotension, and hypertension to determine the singular and combined, transient and steady-state effects of these variables on airway diameter. Breath-by-breath changes in airway size will be measured from pressure changes within the cuffs surrounding tubes located in various airways. These changes will be compared with simultaneous measurements of airway resistance and the mechanical and electrical activity of isolated tracheal muscle in vivo in anesthesthetized dogs. Similarly, continuous, on line changes in airway diameter as manifested by endotracheal tube cuff pressure changes in pre-operative and intraoperative patients will be compared to airway resistance measured by forced oscillation techniques in these patients. The data will be compared with those from the animal studies which will provide a better understanding of factors involved in physiological and pathological alterations of tracheobronchial muscle tone, and will clarify the role of broncho-bronchial reflexes in the regulation of the distribution of an inspirate within different lung regions.